DESCRIPTION: Although there is a great deal known about the transport of proteins into the nucleus, little is known about the mechanisms that direct DNA molecules within this organelle. Recent experimental findings by the PI have suggested that the genomes of large DNA viruses are deposited in or adjacent to defined domains called N10 within the nucleus. Within these domains, virus replication and transcription can begin without the expression of other virus proteins. If N10 domains can be shown to be the obligatory target of large DNA virus genomes, then strategies to block this targeted transport could prevent virus replication. The applicant will construct cell lines in which the N10 target has been eliminated, to test this hypothesis.